肾性高血压大鼠胰岛素抵抗与肾间质纤维化相关研究

Study on the relationship between insulin resistance and renal interstitial fibrosis in rats with renal hypertension

目的从肾素-血管紧张素系统(RAS)角度初步探讨胰岛素抵抗(IR)对肾性高血压大鼠肾间质纤维化的影响。方法SD大鼠行"两肾一夹"手术后随机分为蔗糖喂养组和对照组,蔗糖喂养组蔗糖喂养,对照组正常饲养,18周后处理。于处理前1日测定24h尿蛋白定量;处理日测定2组血浆空腹血糖、胰岛素、胰岛素敏感指数、肾素、血管紧张素Ⅱ、醛固酮、尿素氮和肌酐水平。结果与对照组相比,蔗糖喂养组空腹胰岛素水平明显增高(P<0.01),胰岛素敏感指数水平明显降低(P<0.01),血浆肾素、血管紧张素Ⅱ、醛固酮、尿素氮和肌酐水平及24h尿蛋白定量均明显高于对照组(P<0.01)。相关分析显示,24h尿蛋白定量与血浆空腹胰岛素、胰岛素敏感指数、醛固酮及尿素氮水平呈明显相关。结论IR状态能够加速肾性高血压大鼠肾间质纤维化的损害,除与血压升高、胰岛素的直接促增殖作用有关外,还可能与HIS引起的肾组织局部RAS的激活有关。

Objective To study the possible mechanisms of insulin resistance inducing renal interstitial fibrosis in rats with renal hypertension in accordance with renin-angiotensin system（RAS）. Methods All rats were performed ＂two-kidney one-clip＂ operation to set up renal hypertension model（2K1C RH model） , and were randomly assigned to high sucrose fed group and control group. All rats were sacrificed after 18 weeks . The 24 h urine protein was measured at the day before sacrificed. Fasting blood glucose, insulin, insulin sensitivity index, renin angiotensin, angiotonin, aldosterone, urea nitrogen and creatinine in plasma were measured respectively at the day of sacrificed. Results Renin angiotensin, angiotonin, aldosterone, urea nitrogen, creatinine and 24 h Urine protein in high sucrose fed group were higher than those of control group（ P 〈 0.01） . Correlation analysis indicated that the plasma levels of insulin, insulin sensitivity index, aldosterone and urea nitrogen were significant correlated with 24 h Urine protein. Conclusion Insulin resistance can accelerate the proceeding of renal interstitial fibrosis in HR rats. Besides its direct effect of promoting proliferation through INS and the elevated blood pressure, Insulin resistance maybe generate the indirect effect of promoting the activation of the renin angiotensin system in the parts of renal interstitium through HIS.